This invention relates to apparatus and method for measuring pupillary response parameters, particularly for diagnostic purposes.
The study of pupillary movement in the eyes of humans and animals has evolved considerably over the past hundred years. Physicians and scientists alike have utilized the dynamics of the pupil as a unique and sensitive indicator for a wide range of neurological and physiological process. An early attempt at a recording of this movement was the work of Bellarminov (Pflugers Arch. ges. Physiol., 37, 7, 1885). By placing a glass rod in front of the eye which was illuminated from the side, a dispersed image of the pupil was formed. This image was subsequently recorded continuously on film. Cinematographic techniques using ultraviolet radiation first and infrared radiation later were developed by Lowenstein et al. (Pupillographic Studies, Arch. of Ophthal., 25, 969-993, 1942). This method permitted simultaneous filming of both eyes, and by measuring the individual film frames, a plot of pupil diameter versus time was obtained. However, this technique had several drawbacks, including poor time resolution due to slow frame rates, the use of expensive IR film, and the large amount of manual processing time required.
Some of these difficulties were overcome by a device developed by Lowenstein and Lowenfeld (Electronic Pupillography, AMA Arch. of Ophthal., 59, 352-363, 1958). This device used a rotating drum to project successive infrared beams horizontally across the eye. Since the iris reflects IR radiation better than the pupil, each horizontal sweep across the eye would result in a reflected square pulse with a duration proportional to the distance across the pupil at that point. Electronic circuitry converted the maximum pulse duration (corresponding to the diameter of the pupil) into a voltage which was then recorded. By utilizing this technique, the instrument was able to measure changes in pupil diameter as small as 0.025 mm as well as provide a plot of pupil diameter versus time automatically. However, the device was expensive and cumbersome for use in a clinical applications and was limited in time resolution due to the mechanical scanning involved.
Ishikawa et al. (A New Videopupillography, Ophthalmalogica, 160, 248-259, 1970), developed an instrument to measure the pupil area using a closed-circuit IR television system. Through proper calibration, the pupil area measurement was then converted to one of pupil diameter. This particular system used approximately the same type of horizontal slice imaging introduced by Lowenstein with an improved accuracy of 500 slices/frame and an enhanced time resolution of up to 100 frames/sec. One principal advantage of this approach was the ability to display the video signal on a monitor, which facilitated optical alignment of the subject with respect to the system.
A more recent innovation in TV systems of this type included the development of a single horizontal scan line pupillometer which, when properly aligned, directly detects the pupil diameter (Matsunaga, A New Binocular Electronic Scanning Pupillometer, Physiologia, 16, 115-120, 1973). The move towards single line imaging was initiated by the presence of signal artifacts due to anomalies such as drooping eyelids. Some of the problems inherent in this particular device, such as image lag and distortion, have been removed with the development of a solid-state TV pupillometer (see Watanabe, A Solid State Television Pupillometer, Vision Research, 22, 499-505, 1982).
In general, IR television pupillometers provide very good results. However, the quality of electro-optic components necessary to provide such results makes the systems rather expensive for clinical applications. Also, the fastest frame rates reported in the literature of 100 frames/sec (corresponding to a 10 ms time resolution) has still not been shown to be precise enough for an accurate clinical determination of important parameters describing pupillary movement.
Some research has been directed towards building more cost-effective pupillometers. Jones et al. (A New Solid State Dynamic Pupillometer Using A Self-Scanning Photodiode Array, Journal of Physics E: Scientific Instruments, 16, 1169, 1983) developed a dynamic IR pupillometer utilizing a 100-element linear self-scanning photodiode array to measure the diameter of the pupil. While fairly inexpensive and accurate, this device is limited in time resolution to 20 ms due to rise time constraints of the photodiode array.
A method of monitoring pupil dynamics through detection of pupil area was set forth by Stark (Stability, Oscillations, And Noise In The Human Pupil Servomechanism, Proceedings of The IRE, November 1959). Illumination of the eye with IR radiation results in a reflected signal which is proportional to the iris area. For a fixed detector field of view, the signal is therefore also proportional to the pupil area. While not yielding a direct measurement of pupil diameter, this approach can provide accurate quantitative evaluations of various dynamic pupil movements at a great reduction in complexity and cost (in comparison to the TV systems). An earlier device which monitored pupil area using an IR-sensitive solid-state sensor to detect reflected radiation from the eye was disclosed by Zuber et al. (A Simple Inexpensive Electronic Pupillometer, Vision Research, 5, 695-696, 1965). This device was used to illustrate the instability oscillations in the pupil area due to the presence of a light stimulus on the edge of the iris/pupil interface. A similar device by Cassady was used to monitor changes in the pupil area of paralyzed cats, but was never applied to human subjects (see Cassady, Pupillary Activity Measured By Reflected Infra-Red Light, Physiology And Behavior, 28, 851-854, 1982).
The patent literature also contains examples of instruments and methods for measuring pupillary and other eye characteristics.
U.S. Pat. No. 3,450,466 discloses an eye movement recorder in which a beam is scanned on the surface of an eye and reflected by the eye onto a photomultiplier. The patent states that since the scan is controlled in relationship to the iris and sclera of the eye, the reflected light spot will vary in intensity depending on its relative position on the overall eye surface. The maximum reflected light intensity, and the time of the maximum, are recorded and compared in phase and intensity against a reference, to obtain a record of eye movement.
U.S. Pat. No. 3,473,868 discloses equipment for measuring eye position and movement, and pupil area. Infrared light is reflected off the eye to obtain measurements. In one application of the patented equipment, the upper eyelid is blackened to decrease its reflectivity when it is in the field of view.
U.S. Pat. No. 3,984,156 discloses an eye movement monitoring system which is used in measuring and evaluating a subject's visual field. Determination of whether the subject has seen or missed a particular target is evaluated by logic systems which discriminate between eye movement and positions displaying characteristics indicative of whether the subject has seen or missed the target. The logic discriminates between blinks, hunting eye movements and other characteristic positions and movements which are indicative of the subject having seen the target.
Other U.S. Patents pertaining to eye measurements are U.S. Pat. Nos. 4,149,787, 4,169,663, 4,387,974, 4,397,531 and Re 28,415.
The relationship of pupillary light response ("PLR") to various pathological conditions has been reported by a number of prior art researchers. Alexandridis et al. (The Latent Period of The Pupil Light Reflex In Legions of The Optic Nerve, Ophthalmalogica, Basel, 182, 211-217, 1981) have shown a distinct prolongation in PLR latency (i.e., the time lag between stimulus and the onset of pupillary constriction) associated with optic nerve inflammation or atrophy. It was originally thought that this increase in the latency was due to the loss of sensory perception accompanying such abnormalities. Lowering the stimulus intensity incident on a normal eye increases the PLR latency while the PLR response amplitude and maximum speed of contraction decrease (see Lowenfeld et al., Influence of Pupil Size on Dynamics of Pupillary Movements, Amer. Jour. of Ophthal., 71, 347-362, 1971). People who suffer from abnormalities of the optic nerve generally have higher sensory thresholds, meaning that more light is required to obtain the same response (visual or pupillary) as a normal eye. Consequently, people with this condition generally have a diminished PLR similar to that obtained with a normal eye at a lower stimulus intensity. Thus, a loss of sensory perception can account for a slight increase in pupillary latency as well as the other characteristics of a diminished reflex. However, the findings of Lowenfeld et al. determined that the prolonged latency in cases of optic nerve inflammation or atrophy was beyond that to be expected from a loss of sensory perception alone. In fact, the Lowenfeld et al. study used the degree of prolongation in the latency to diagnose the type as well as the location of the neuropathy involved.
C. Ellis, in Journal of Neurology, Neurosurgery, and Psychiatry, 42, 1008-1017, 1979, presents a history of measurement and use of pupillary reaction, and a study of pupillary responses of patients with acute optic neuritis. In a study described by Ellis, an infrared television pupillometer was used. The pupillary diameter was measured from the television video frames using a pupillometer analyser system. The limit of resolution of timed events (presumably, the time between successive video frames) was 20 ms and the resolution of pupillary diameter was 0.03 mm. Subjects were dark adapted, and a 100 ms white light stimulus, focused to a 2.0 mm beam was delivered every eight seconds. Among other things, Ellis measured latency from stimulus to onset of pupillary constriction and maximum rate of pupillary constriction. It was found that patients with acute optic neuritis had prolonged latency in most cases. However, Ellis observed that the latency data was limited by the resolution of the equipment, and by the difficulties of defining exactly the onset of pupillary constriction.
Amblyopia, the "lazy eye syndrome" is another eye defect that increases the PLR latency. A study by Kase et al. (Pupillary Light Reflex in Amblyopia, Invest. Ophthal. and Vis. Sci, 467-471, 1981) using an infrared TV-camera based instrument with time resolution of 16 ms, showed that 10 of 15 patients with amblyopia had significant increases in latency (both direct and consensual) when the affected eye was stimulated. The remaining 5 has no measurable latency differences between the normal and affected eye. The fact that both eyes were affected equally upon stimulus of the damaged eye signifies that amblyopia is an afferent defect (retina to brain) and not an efferent impairment (brain to iris). The PLR amplitude and speed of constriction did not differ significantly from the values measured when the normal eye was stimulated. Also, there was no correlation between an increase in pupillary latency and a loss of visual acuity indicating separate sites and mechanisms for these two conditions. This might explain why most people do not notice the presence of amblyopia until detected clinically.
The presence of a normal PLR has been used subjectively for a long time in accessing the severity of intracranial damage. One study by Braakman et al. (Systematic Selection of Prognostic Features In Patients With Severe Head Injury, Neurosurgery, 6, 362-369, 1980) on the prognostic indicators of patients with severe head injuries showed the presence of a PLR to be highly-correlated with the survival rate of those patients. A similar study reported in the American Medical News Mar. 15, 1985, p.55) determined the PLR to be a good clinical assessment of possible recovery in coma patients. In this latter report, none of the 52 patients who showed no response to light ever recovered to "independent daily function." In contrast, 11 out of 27 patients who did show response to light regained independence in their daily lives.
A unilateral sluggish pupil has been reported as a sign of brain herniation, a stroke-causing condition (see AFP, Vol. 31, No. 3, page 192).
From the above, it is seen that prior investigators have recognized various possibilities in using pupillary response as a diagnostic tool. However, except for traditional relatively crude determinations (e.g. checking the pupils of a patient with a flashlight), sophisticated use of pupillary response parameters has not found widespread use in applications where it is believed to have tremendous potential; viz., in diagnosing the onset or presence of injury or disease, and in determining the presence of drugs or alcohol in the body. A primary reason for this lack of development is that prior art techniques and systems suffer from one or more of the following disadvantages:
(a) The cost of obtaining pupillary measurements, is high, since accurate equipment has tended to be relatively expensive to purchase and/or use.
(b) The resolution of the measurement of pupillary response is often not sufficient to permit determination of pupillary response parameters with accuracy that is needed for diagnosis.
(c) Artifacts in the measurement of pupillary response prevent obtainment of true pupillary response parameters that would provide a meaningful indicator of physical condition.
It is among the objects of the present invention to provide a method and apparatus for determination of pupillary response that overcomes problems of prior art techniques and systems.